Pegylation

Chemical linking of proteins with polyethylene glycol (PEG) to protect these proteins from degradation processes in the body.

Proteins are pegylated by attaching the polyethylene glycol molecule (PEG) to the protein. This is achieved by a stable, covalent bond between an amino or also sulfhydryl group of the protein and a chemically reactive group (e.g. ester, aldehyde) of the polyethylene glycol. The resulting structures can be linear or branched. The reaction is influenced by factors such as type of protein as well as reaction time, temperature, pH-value. For this reason, the appropriate polyethylene glycol must be determined for each therapeutic molecule. By means of the pegylation process, therapeutic proteins, which are given intravenously, can be modified to achieve better stability, half-life, water solubility, etc. Even tiny polyethylene glycol molecules with a size of 40-50 kDa are sufficient to enlarge smaller molecules in such a way that filtration from the kidney tissue is made more difficult, which consequently leads to a longer body residence time. Proteins enveloped by the attached PEG molecules can thus be additionally protected from the degradation of the body's own enzymes. Polyethylene glycol is non-toxic and amphophilic, which means that they are soluble in water as well as in most organic solvents. Virtually every molecule on earth can be altered in this way. In addition to therapeutic proteins and peptides such as growth factors or blood derivatives in medicine, liposomes used in food or cosmetics can also be pegylated. In this way the human being is exposed to daily contact with polyethylene glycol (see below contact allergy). A prominent example in medicine is the pegylation of interferon alfa-2a.